We propose two Specific Aims for Core Research: Specific Aim #1: Apply principles of mechanistic ion chemistry to seek an understanding of the fragmentations ov various classes of biomolecules and their interactions with other molecules, radicals, and ions. The sub-aims focus on lipids and charge-remote fragmentations; DNA bases and oligonucleotides; peptide/metal-ion interactions; H/D exchanges of peptide bound to proteins; reactions of biomolecules ions with radicals; and fragmentation of small molecules upon electron capture. Specific Aim #2: Improve the performance of Fourier transform (FT) by adding the RF-only-mode, which allows operation at relatively high pressure, and the electrically compensated cell. This aim is centered on the development of a superconducting FT mass spectrometer for matrix- assisted laser desorption ionization (MALDI), which should be of interest to many users of this Resource. The addition of the RF-only-mode event will allow the unique instrument to be used in a single experiment as both an ion trap (quistor) and a FTMS ion trap, taking advantage of the features of both. We will continue to develop foundations for instrument improvement (i.e., scaling, frequency focusing, and RF-only-mode stability) and apply strategies that emerge from the foundations to modify a Finnigan FT mass spectrometer with a 3-Tesla magnet and a MALDI source. For collaborative research we propose on Specific Aim (No. 3) to continue collaborations with biomedical investigators to provide new or improved measurement strategies to enable advances in the understanding of various disease stages: diabetes mellitus, atherosclerotic cardiovascular disease; alcohol abuse; malignant neoplastic disease, (particularly breast, skin, and bladder cancers), acquired immunodeficiency syndrome (AIDS), gerontology and aging, obesity and its complications and treatment, protein deprivation and malnutrition. This understanding will be sought by using a variety of now resident mass spectrometers (ion- trap, triple quadrupole, quadrupole, isotope-ratio, FT, magnetic-sector, and time-of-flight) and ionization methods (particularly electrospray, ESI, but also MALDI, fast atom analytes and of H/D exchange of biomolecules will be conducted with a new quadruple/TOF tandem spectrometer, for which funds are requested. Most of the current instrument capabilities were put in place since 1994 during major reorganization of staff and research goals of this Resource.